|
British Journal of Pharmacology
|
|
|
January 1999, Volume 126, Issue 1, Pages 147 - 158 |
|
|
Journal Home |
||
| <- Previous | Issue Contents | Next -> |
| Original Article |
|
Neuroregulation by vasoactive intestinal peptide (VIP) of mucus secretion in ferret trachea: activation of BKCa channels and inhibition of neurotransmitter release
Yu-Chih Liu2, Hema J. Patel1, Aamir M. Khawaja1, Maria G. Belvisi1,4 & Duncan F. Rogers1,3 1Thoracic Medicine, National Heart & Lung Institute (Imperial College), Dovehouse Street, London SW3 6LY, U.K. 2Thoracic Medicine, Chang Gung Memorial Hospital, 199 Tun-Hwa North Road, Taipei, Taiwan, R.O.C.3Author for correspondence: E-mail: duncan.rogers@ic.ac.uk 4Current address: Pharmacology, Rhône-Poulenc Rorer, Rainham Road South, Dagenham, Essex RM10 7XS. |
| Keywords |
| Acetylcholine release;
airways;
cholinergic nerve;
ferret trachea;
iberiotoxin;
mucus secretion;
potassium channel;
vasoactive intestinal peptide |
| Abstract |
1 The aims of this study were to determine: (1) whether vasoactive intestinal peptide (VIP) regulates cholinergic and `sensory-efferent' (tachykininergic) 35SO4 labelled mucus output in ferret trachea in vitro, using a VIP antibody, (2) the class of potassium (K+) channel involved in VIP-regulation of cholinergic neural secretion using glibenclamide (an ATP-sensitive K+ (KATP) channel inhibitor), iberiotoxin (a large conductance calcium activated K+ (BKca) channel blocker), and apamin (a small conductance Kca (SKca) channel blocker), and (3) the effect of VIP on cholinergic neurotransmission using [3H]-choline overflow as a marker for acetylcholine (ACh) release. 2 Exogenous VIP (1 and 10 µM) alone increased 35SO4 output by up to 53% above baseline, but suppressed (by up to 80% at 1 µM) cholinergic and tachykininergic neural secretion without altering secretion induced by ACh or substance P (1 µM each). Endogenous VIP accounted for the minor increase in non-adrenergic, non-cholinergic (NANC), non-tachykininergic neural secretion, which was compatible with the secretory response of exogenous VIP. 3 Iberiotoxin (3 µM), but not apamin (1 µM) or glibenclamide (0.1 µM), reversed the inhibition by VIP (10 nM) of cholinergic neural secretion. 4 Both endogenous VIP (by use of the VIP antibody; 1 : 500 dilution) and exogenous VIP (0.1 µM), the latter by 34%, inhibited ACh release from cholinergic nerve terminals and this suppression was completely reversed by iberiotoxin (0.1 µM). 5 We conclude that, in ferret trachea in vitro, endogenous VIP has dual activity whereby its small direct stimulatory action on mucus secretion is secondary to its marked regulation of cholinergic and tachykininergic neurogenic mucus secretion. Regulation is via inhibition of neurotransmitter release, consequent upon opening of BKCa channels. In the context of neurogenic mucus secretion, we propose that VIP joins NO as a neurotransmitter of i-NANC nerves in ferret trachea. |
Received 18 May 1998; Revised 9 October 1998; Accepted 13 October 1998
